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THE NUCLEUS - Coggle Diagram

- - - - mRNA - messenger (genes)
      - rRNA - ribosomal
      - tRNA - transfer (protein synthesis)
      - Assembled ribosomal subunits
  - - - Passive transport: small molecules and proteins (up to ~40 kDa)
      - Facilitated transport: RNAs, larger proteins, macromolecular complexes
        
        requires nuclear transport receptors: karyopherins
      - FACILITATED TRANSPORT REQUIRES ENERGY
        
        ATP hydrolysis for mRNA
        
        GTP hydrolysis for proteins, tRNA and ribosomes
    - - mRNP: mRNA-protein complex
        
        includes processing, capping, splicing proteins as well as export factors
        
        mRNP can go out or in through NPC
        
        ATP hydrolysis :arrow_right: release of Dbp5 in cytoplasm and mRNP remodlling
        
        energy is needed to maintain a gradient: net movement of molecules from across barrier, rather than coming to equilibrium
  - - - bind cargo proteins in cytoplasm
      - interact with FG-Nups
      - release cargos in nucleus
    - - conformational change that results in complex coming apart
  - - - bind cargo proteins in nucleus
      - interact with FG-Nups
      - Release cargos in cytoplasm
    - - Conformational change that results in complex assembly
    - - GTPases are molecular switches
        
        Small GTPases (Ran, Ras, Rho and other families) bind GTP, hydrolyse a phosphate group :arrow_right: GDP
        
        not very good at hydrolysing
        
        FTP/GDP :arrow_right: conformational change in the GTPase :arrow_right: bind or unbind proteins
        
        GTP hydrolysis GDP assisted by GAP proteins (GTPase activating proteins)
        
        Ran-GAPs in the cytosol
        
        Ran-GDP is quickly disassembled by GAP
        
        GTP loading after hydrolysis by GEFs (guanine nucleotide exchange factors)
        
        Ran-GEFs in the nucleus
        
        Ran-GTP is quickly loaded dt. GEF presence
        
        Difference between Ran-GTP and Ran-GDP in nucleus vs cytoplasm maintains gradient for import-export
  - - - Protein motif typically 8 amino acids long
      - can occur anywhere in the protein
      - many basic residues (AAs) such as lysine (K), arginine (R), and proline (P)
      - Binds to importins
    - - sequence with four hydrophobic amino acids (most often leucine, L)
      - eg LxxxLxxLxL, where x is any other amino acid
      - Binds to exportins
- - - - Storage of DNA, genetic template ('hard drive')
      - Transcription of RNA from DNA - conversion of information from storage into usable information ('RAM')
      - Mechanical element - stiffer than the rest of the cell
      - Eukaryotes: genetic material is compartmentalised
        
        Benefits of Compartmentalisation
        
        protect DNA - critical information storage from lysosomes/peroxisomes
        
        increase surface area for membrane-localised reactions
        
        increase efficiency of transcription and synthesis
        
        more ways to regulate gene expression
        
        most cells have one nucleus, with some exceptions
        
        red blood cells (none)
        
        skeletal muscle (many)
    - - invagination occurs at some point
        
        fusion around DNA into nucleus
        
        nucleus
        
        inside the nucleus is topologically continuous with the inside of the cell (evidence)
        
        endoplasmic reticulum
        
        inside of ER is similar to extracellular matrix (evidence)
        
        nuclear pore
        
        inner nuclear membrane
        
        outer nuclear membrane
  - - - inner membrane space is continuous with lumen of ER
      - ER: endoplasmic reticulum
        
        site of protein production by ribosomes
        
        protein folding
        
        glycosylation (adding sugar molecules)
      - Double membrane continuous with membrane of ER
    - - lamina: thin plate, slice, layer (laminate floor)
      - NUCLEAR LAMINS
        
        related to intermediate filaments
        
        for meshwork attached to inner nuclear membrane (structural)
        
        associate with DNA (functional
        
        2 types: A/C (cleaved from A) and B
        
        Laminopathies (mutations) :arrow_right: muscular dystrophy (no structural integrity to protect DNA) and progeria
      - IS CONNECTED TO THE CYTOSKELETON
        
        important for stability and also information transfer (LINC complex between Nesprin - SUN/KASH - lamin)
        
        protein complex that links nuclear lamina with cytoskeleton
        
        inner membrane: SUN/KASH proteins
        
        Outer membrane: nesprins
        
        Each of 4 types of nespins connect to specific structures of the cytoskeleton
    - - "nucleoskeleton"
      - NuMa: nuclear mitotic apparatus 1; very large (238 kDa); organisation of chromatin
      - Titin: binds chromosomes and lamina
      - Spectrin: elastic component of lamina
      - PLF: pore-linked filaments
      - Nuclear actin: short filaments or monomeric (G-actin)
      - Motor proteins: nuclear myosin, kinesics
  - - - Euchromatin:
        
        true chromatin
        
        less visible by microscopy
        
        not so densely packed
        
        majority of genome (~90%)
        
        localised in central part of nucelus
      - Heterochromatin:
        
        different chromatic
        
        looks dark under the microscope
        
        tightly-packed condensed DNA
        
        localised around lamina and nucleoli
      - SPATIAL ARRANGEMENT OF CHROMATIN
        
        LADs: Lamina-Associated Domains
        
        "B" type chromatin = heterochromatin ("A" = euchromatin)
        
        Low level of RNA transcription in LADs
        
        TADs: Topologically Associated Domains
        
        bundles of chromatin that form an Active compartment and Recessive compartment
        
        lots of overlap with gene expression
        
        TADs formed by cohesion
        
        Singh-shaped protein complez
        
        Physically bundles chromatin
        
        TAD boundaries formed by CTCF
        
        CCCTC-binding factor
        
        Transcription factor expressed in all cell types
        
        Insulated neighbourhoods
        
        Co-regulation of genes in that region
        
        One or more per TAD
        
        Enhancer: far away linearly, close spatially
  - - - Major functions:
        
        Transcription of rRNAs
        
        Assembly of ribosomal subunits
      - Composed of:
        
        segments of 10 chromosomes encoding rRNA genes
        
        proteins for processing rRNAs
        
        ribosomal subunit protiens
        
        Small nucleolar RNA (snoRNA) oligonucleotides that help process rRNAs
      - Other functions:
        
        sensing and responding to stress
        
        cell cycle regulation
        
        cancer
    - - 0.2-2um diameter
      - RNA processing
      - genome organisation (chromosome domain boundaries)
      - dense foci of Colin protein - resemble coiled balls of yarn under EM
    - - 0.1-1um diameter
      - often associated with Cajal bodies
      - DNA repair, cell proliferation, programmed cell death
    - - 20nm - 1um diameter
      - Gene transcription
      - mRNA processing (splicing to make various versions of genes